rs11247593

Variant names:

• chr1-26725589-G-A
• rs11247593
• NM_006015.6:c.1138-4062G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-26725589-G-A
• chr1-26725589-G-C
• chr1-26725589-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006015.6(ARID1A):​c.1138-4062G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 151,956 control chromosomes in the GnomAD database, including 9,487 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (9487 hom., cov: 31)
• Consequence: ARID1A NM_006015.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.175
• Publications: 7 publications found

Genes affected

ARID1A (HGNC:11110): (AT-rich interaction domain 1A) This gene encodes a member of the SWI/SNF family, whose members have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI, which is required for transcriptional activation of genes normally repressed by chromatin. It possesses at least two conserved domains that could be important for its function. First, it has a DNA-binding domain that can specifically bind an AT-rich DNA sequence known to be recognized by a SNF/SWI complex at the beta-globin locus. Second, the C-terminus of the protein can stimulate glucocorticoid receptor-dependent transcriptional activation. It is thought that the protein encoded by this gene confers specificity to the SNF/SWI complex and may recruit the complex to its targets through either protein-DNA or protein-protein interactions. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ARID1A Gene-Disease associations (from GenCC):

• Coffin-Siris syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• intellectual disability, autosomal dominant 14

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Illumina, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID1A	NM_006015.6	c.1138-4062G>A		intron_variant	Intron 1 of 19	ENST00000324856.13	NP_006006.3
ARID1A	NM_139135.4	c.1138-4062G>A		intron_variant	Intron 1 of 19		NP_624361.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARID1A	ENST00000324856.13	c.1138-4062G>A		intron_variant	Intron 1 of 19	1	NM_006015.6	ENSP00000320485.7

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47317 AN: 151838 Hom.: 9475 Cov.: 31

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.929

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.342

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.312 AC: 47353 AN: 151956 Hom.: 9487 Cov.: 31 AF XY: 0.321 AC XY: 23868 AN XY: 74282

African (AFR) AF: 0.357 AC: 14772 AN: 41418

American (AMR) AF: 0.494 AC: 7538 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 761 AN: 3472

East Asian (EAS) AF: 0.929 AC: 4811 AN: 5176

South Asian (SAS) AF: 0.498 AC: 2395 AN: 4814

European-Finnish (FIN) AF: 0.198 AC: 2085 AN: 10546

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.205 AC: 13957 AN: 67958

Other (OTH) AF: 0.349 AC: 735 AN: 2104

Alfa AF: 0.246 Hom.: 13649

Bravo AF: 0.338

Asia WGS AF: 0.686 AC: 2385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	10
DANN	Benign	0.63
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11247593; hg19: chr1-27052080;